The ability to quantify thermal dosage is essential if hyperthermia is to be used for the treatment of cancer. However, no acceptable method yet exists. The solution to this problem demands major advances in two areas: a) the accurate three dimensional measurement (or calculation) of tissue temperatures (temperature mapping) and b) the conversion of these measurements into a treatment description which is a predictor of response. While the first area is beyond the scope of this project, the goal of this proposal is to address the second of these problems by furthering the development of a clinically useful means of calculating thermal dose from time and temperature information gathered during hyperthermia therapy. Towards this goal, a simple thermal dose calculating method was developed and described by the principal investigator. A number of clinical reports, both in human trials and in trials on spontaneous tumors in pet animals have shown that this method is predictive of response and may be the best approach available. This proposal is directed toward improving and adapting this approach to account for some of the factors which are known to influence thermal effects and will also attempt to investigate alternative means of quantifying thermal treatments. These directions are reflected in the following four specific aims: 1) The first aim is to further develop thermal iso-effect dose concepts and calculations to account for the phenomena of a) step-down heating, b) thermal adaptation and c) thermotolerance. To this end, in vitro data will be obtained to provide the information necessary for the mathematical description of these phenomena. In vivo testing of these improvements will be performed using murine normal bone marrow and tumors. 2) The second aim is to investigate the time-temperature relationship when hyperthermia is combined with radiation or chemotherapeutic agents. 3) The third aim is to investigate the importance of spatial distribution of thermal dose in the response to clinical treatment and to evaluate methods of describing the spatial distribution of dose by using a murine tumor system where predictable thermal gradients can be reproduced. 4) The fourth aim is to develop, distribute and maintain a Hyperthermia Data File Standard format and computer programs which can be used to evaluate dose models by any institution with actual clinical data.